Botulinum A toxin (Botox) is used for the treatment of many muscular dystonias. However, the relief of the sustained and abnormal postures induced by Botox administration is not fully explained. In this work the possibility was considered that Botox can produce a block not only at the alpha motor endings, but also at the gamma motor endings, consequently reducing the spindle inflow to the alpha motoneurons, which have a great role in maintaining the tonic myotatic reflex. Jaw muscle spindle discharge was recorded before and after Botox injection in the deep masseter muscle. The drug consistently reduced the spindle afferent discharge. Such an effect is suggested to be direct on gamma endings as: i) muscle tension was not modified by Botox during the recording time; ii) saline administration never changed the spindle discharge. The Botox effect on muscle spindles suggests that the relief from dystonias could be due not only to a partial motor paralysis, but also to a decrease of the reflex muscular tone.

SUMMARY1. Eye movements in unanaesthetized rabbits were studied during horizontal neck-proprioceptive stimulation (movement of the body with respect to the fixed head), when this stimulation was given alone and when it was given simultaneously with vestibular stimulation (rotation of the head-body). The effect of neckproprioceptive stimulation on modifying the anticompensatory fast-phase eye movements (AFPs) evoked by vestibular stimulation was studied with a 'conditioningtest ' protocol; the 'conditioning' stimulus was a neck-proprioceptive signal evoked by a step-like change in body position with respect to the head and the 'test' stimulus was a vestibular signal evoked by a step rotation of the head-body.2. The influence of eye position and direction of slow eye movements on the occurrence of compensatory fast-phase eye movements (CFPs) evoked by neckproprioceptive stimulation was also examined.3. The anticompensatory fast phase (AFP) evoked by vestibular stimulation was attenuated by a preceding neck-proprioceptive stimulus which when delivered alone evoked compensatory slow-phase eye movements (CSP) in the same direction as the CSP evoked by vestibular stimulation. Conversely, the vestibularly evoked AFP was potentiated by a neck-proprioceptive stimulus which evoked CSPs opposite to that of vestibularly evoked CSPs.4. Eccentric initial eye positions increased the probability of occurrence of midline-directed compensatory fast-phase eye movements (CFPs) evoked by appropriate neck-proprioceptive stimulation.

Injections of botulinum toxin type A (BoTox) in one extraocular muscle (EOM) induce long lasting paretic lengthening of the muscle permitting realignment to occur in strabismus, while eye movements appear to be unaffected after the transitory period of induced paresis. It has been hypothesized a BoTox-induced change in the spindle discharge of EOMs to explain the effect in EOM length. In decerebrate lambs and goats, first order neurons of eye muscle spindles were identified in a cellular pool located in the medial dorsolateral portion of the semilunar ganglion. The belly of the muscle to which the recorded unit belonged was infiltrated with BoTox. A decrease in afferent discharge of the spindle and in its stretch sensitivity was observed. This effect began 10-15 minutes after the injection. There was no corresponding decrease in muscle tension during the first 45 minutes. This finding suggests that the block of release of acetylcholine at motor endings is earlier and more efficacious in gamma- than in alpha-motoneurons. As a result of the proprioceptive input reduction, an unbalance between the agonist and antagonist muscles should occur favouring the ocular realignment.

The cervico-ocular reflex (COR) was studied alone or in combination with the vestibulo-ocular reflex (VOR) in the rabbit. Step stimulations of the body with respect to the fixed head induced small slow compensatory responses followed by large compensatory quick phases (QP). These responses remained aligned with the horizon at different head pitch angles. The QP reorientation in space was due to the gravity influence on the otolithic receptors. The vestibular induced QPs exhibit a similar pattern. Because of this reorientation, the reduction of the amplitude of the vestibular induced QPs, due to the addition of the COR, was maintained even at different static head positions. The electrolytic lesion of the ophthalmic branch of the trigeminal nerve deeply affected the space orientation of the COR. In particular, the cervically induced compensatory QPs of the eye ipsilateral to the lesion showed a remarkable variability of their trajectories and they lost space reorientation. These findings suggest that the coordinate system controlling the QPs is influenced by signals originating from both head position in space and eye position in the orbit.

The purpose of this study was to assess whether vestibulotoxicity caused by aminoglycoside antibiotics is influenced by the treatment schedule used: i.e., a single high dose given once daily (o.d.) vs multiple divided doses (tres in die, t.i.d.). Two groups of guinea pigs (5 animals/group) were injected intramuscularly for 21 days with either netilmicin or amikacin 150 mg/kg o.d., whereas other groups received each drug at 50 mg/kg t.i.d. at 8-h intervals. Amikacin was also given at 225 mg/kg o.d. and 75 mg/kg t.i.d. Vestibular functions were assessed by measuring vestibulo-ocular reflexes. Acoustic function was also evaluated by measuring Preyer's pinna reflex. Sensory epithelia of the inner ears were evaluated histologically under a scanning electron microscope. Netilmicin failed to affect either the vestibular or the acoustic apparatus in the animal groups receiving the two dosing regimens. Amikacin in a dose of 150 mg/kg per day induced an acoustic deficit which was more severe in the t.i.d. group. The higher dose of amikacin provoked significant lesions of acoustic and vestibular function, irrespective of the dosing regimen used. These data suggest that the o.d. dosing regimen of the aminoglycoside antibiotics might provide effective treatment for infectious diseases without enhancing the risk for vestibular and acoustic side effects.